DESCRIPTION: (Principal Investigator's) The aims of this proposal are the design, preparation and comparative testing of versatile polymeric supports that will offer new opportunities for faster, more efficient and chemically diverse, or larger scale solid phase syntheses of combinatorial libraries of biologically active compounds. The major targets include functional organic polymers with optimized shapes, sizes, capacity, crosslinking densities, porosities, and chemistries. These materials will be designed to complement th currently available supports while providing substantially improved performanc in the preparation of combinatorial libraries as a result of their increased versatility, capacity, batch-to-batch reproducibility, and the suitable combination of both bulk and surface chemistry. Specifically, we plan to explore gel and macroporous beads as well as monolithic supports and shaped objects. Our approach to spherical size monodisperse supports will involve bot commercially available and specialty monomers. The preparation of larger uniformly sized beads (200 microm to 1 mm) will involve the development of totally new preparative procedures for easier scale-up. The use of large monolithic supports and shaped objects will provide new opportunities such as simple tracking, ease of handling within the automated devices, high loading capacity, and work in a flow-through regime. The development of supports with new chemistries is one of our most important objectives. In addition to the direct use of non-traditional monomers, such as methacrylates and substituted styrenes, spatially targeted modification reactions will result in supports allowing unique tagging with metal ions. Original photoactive linkers will als be developed for a broad spectrum of supports. New 3-dimensional multifunctional linkers will enhance capacity and facilitate reactions within the space of the pores. Polymer-supported auxiliaries such as solid-phase reagents, scavengers, catalysts, quenchers, and cosolvents that simplify liquid-phase combinatorial syntheses are another target of this proposal. Overall, the availability of optimized supports in a variety of formats will contribute to the discovery of new leads and accelerate the transfer of new drugs to testing and manufacturing.